Regeneron Announces FDA Acceptance of EYLEA® (aflibercept) Injection Supplemental Biologics
`License Application for Review for Diabetic Macular Edema Indication
`
`December 18, 2013
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`TARRYTOWN, N.Y., Dec. 18, 2013 /PRNewswire/ --  Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that the U.S. Food and
`Drug Administration (FDA) has accepted for standard review the Company's supplemental Biologics License Application (sBLA) for EYLEA®
`(aflibercept) Injection for the treatment of Diabetic Macular Edema (DME). Under the Prescription Drug User Fee Act (PDUFA), the goal for a standard
`review of an sBLA is ten months from submission, for a target action date of August 18, 2014.
`
`"Diabetes is a growing public health concern and DME is a leading cause of vision loss in patients with diabetic retinopathy," said George D.
`Yancopoulos, M.D., Ph. D., Chief Scientific Officer of Regeneron and President of Regeneron Laboratories.  "We hope to be able to offer a new
`treatment option to patients who suffer from diabetic macular edema."
`
`The EYLEA sBLA submission is based on the positive results from the Phase 3 VIVID and VISTA trials.
`
`EYLEA was approved in the United States for the treatment of neovascular (wet) Age-related Macular Degeneration (AMD) in November 2011 and for
`Macular Edema following Central Retinal Vein Occlusion (CRVO) in September 2012.  EYLEA has also been approved in the European Union (EU),
`Japan, Australia, and in several other countries for use in wet AMD.  EYLEA has also been approved by the European Commission for the treatment
`of visual impairment due to macular edema following CRVO, as well as in selected countries in Asia and Latin America.  Regulatory submissions have
`also been made in the EU for EYLEA in DME.
`
`Bayer HealthCare and Regeneron are collaborating on the global development of EYLEA. Regeneron maintains exclusive rights to EYLEA in the
`United States.  Bayer HealthCare licensed the exclusive marketing rights outside the United States, where the companies share equally the profits
`from sales of EYLEA, except for Japan where Regeneron receives a royalty on net sales.
`
`About the EYLEA® (aflibercept) Injection Phase 3 DME Program
`
`The Phase 3 DME program consists of three double-masked trials: VIVID-DME, VISTA-DME, and VIVID-EAST-DME (in Russia, China and other
`Asian countries), and one open-label, single arm safety trial in Japanese patients (VIVID-Japan).  All three double-masked studies have three
`treatment arms, where patients are randomized to receive either EYLEA 2 mg monthly, EYLEA 2 mg every two months (after 5 initial monthly
`injections), or the comparator treatment of laser photocoagulation.  The primary endpoint of all three studies is the mean change in best-corrected
`visual acuity from baseline, as measured on the Early Treatment Diabetic Retinopathy Scale (ETDRS) eye chart, a standard chart used in research to
`measure visual acuity.  The VIVID-DME, VISTA-DME, and VIVID-EAST-DME studies are ongoing.
`
`About Diabetic Macular Edema (DME)
`
`DME is a common complication of Diabetic Retinopathy, a disease affecting the blood vessels of the retina.  Clinically significant DME occurs when
`fluid leaks into the center of the macula, the light-sensitive part of the retina responsible for sharp, direct vision.  Fluid in the macula can cause severe
`vision loss or blindness.
`
`DME is the most frequent cause of blindness in young and mid-aged adults.  According to the American Diabetes Association, over 18 million
`Americans currently suffer from diabetes, and many more are at risk for developing diabetes.  The incidence of diabetes is steadily climbing and it is
`projected that up to seven percent of all patients with diabetes will develop DME during their lifetime.
`
`About EYLEA® (aflibercept) Injection for Intravitreal Injection
`
`Vascular Endothelial Growth Factor (VEGF) is a naturally occurring protein in the body.  Its normal role in a healthy organism is to trigger formation of
`new blood vessels (angiogenesis) supporting the growth of the body's tissues and organs.  However, in certain diseases, such as wet age-related
`macular degeneration, it is also associated with the growth of abnormal new blood vessels in the eye, which exhibit abnormal increased permeability
`that leads to edema.  Scarring and loss of fine-resolution central vision often results.
`
`EYLEA, known in the scientific literature as VEGF Trap-Eye, is a recombinant fusion protein, consisting of portions of human VEGF receptors 1 and 2
`extracellular domains fused to the Fc portion of human IgG1 and formulated as an iso-osmotic solution for intravitreal administration.  EYLEA acts as a
`soluble decoy receptor that binds VEGF-A and placental growth factor (PlGF) and thereby can inhibit the binding and activation of their cognate VEGF
`receptors. 
`
`IMPORTANT PRESCRIBING INFORMATION FOR EYLEA® (aflibercept) INJECTION IN THE UNITED STATES
`
`EYLEA® (aflibercept) Injection is indicated for the treatment of patients with neovascular (Wet) Age-related Macular Degeneration (AMD).  The
`recommended dose for EYLEA is 2 mg administered by intravitreal injection every 4 weeks (monthly) for the first 12 weeks (3 months), followed by 2
`mg once every 8 weeks (2 months).  Although EYLEA may be dosed as frequently as 2 mg every 4 weeks (monthly), additional efficacy was not
`demonstrated when EYLEA was dosed every 4 weeks compared to every 8 weeks.
`
`EYLEA is indicated for the treatment of patients with Macular Edema following Central Retinal Vein Occlusion (CRVO).  The recommended dose for
`EYLEA is 2 mg administered by intravitreal injection every 4 weeks (monthly).
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`Samsung et al. v. Regeneron IPR2023-00884
`Regeneron Pharmaceuticals, Inc. Exhibit 2106 Page 1
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`IMPORTANT SAFETY INFORMATION FOR EYLEA® (aflibercept) INJECTION
`
`EYLEA® (aflibercept) Injection is contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or known
`hypersensitivity to aflibercept or to any of the excipients in EYLEA.
`
`Intravitreal injections, including those with EYLEA, have been associated with endophthalmitis and retinal detachments.  Proper aseptic injection
`technique must always be used when administering EYLEA.  Patients should be instructed to report any symptoms suggestive of endophthalmitis or
`retinal detachment without delay and should be managed appropriately.  Intraocular inflammation has been reported with the use of EYLEA.
`
`Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with EYLEA.  Sustained increases in
`intraocular pressure have also been reported after repeated intravitreal dosing with VEGF inhibitors.  Intraocular pressure and the perfusion of the
`optic nerve head should be monitored and managed appropriately.
`
`There is a potential risk of arterial thromboembolic events (ATEs) following use of intravitreal VEGF inhibitors, including EYLEA, defined as nonfatal
`stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause).  The incidence of ATEs in the VIEW 1 and VIEW 2 wet
`AMD studies in patients treated with EYLEA was 1.8% during the first year.  The incidence of ATEs in the COPERNICUS and GALILEO CRVO studies
`was 0% in patients treated with EYLEA compared with 1.4% in patients receiving sham control during the first six months.
`
`The most common adverse reactions (5% or more) noted in the U.S. prescribing information for the approved indications of EYLEA were conjunctival
`hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and increased intraocular pressure.
`
`Serious adverse reactions related to the injection procedure have occurred in &< 0.1% of intravitreal injections with EYLEA including endophthalmitis,
`traumatic cataract, increased intraocular pressure, and vitreous detachment.
`
`Please see the full U.S. Prescribing Information for EYLEA at www.EYLEA.com
`
`About the EYLEA® (aflibercept) Injection Global Collaboration
`
`Regeneron is collaborating with Bayer HealthCare on the global development of EYLEA.  EYLEA is currently approved for the treatment of wet AMD in
`approximately 50 countries outside the U.S., including Japan and Australia and countries in the EU.  EYLEA has also been approved by the European
`Commission for the treatment of visual impairment due to macular edema secondary to CRVO.
`
`Regeneron maintains exclusive rights to EYLEA in the United States.
`
`About Regeneron Pharmaceuticals
`
`Regeneron is a leading science-based biopharmaceutical company based in Tarrytown, New York that discovers, invents, develops, manufactures,
`and commercializes medicines for the treatment of serious medical conditions.  Regeneron markets medicines for eye diseases, colorectal cancer,
`and a rare inflammatory condition and has product candidates in development in other areas of high unmet medical need, including
`hypercholesterolemia, oncology, rheumatoid arthritis, asthma, and atopic dermatitis.  For additional information about the company, please visit
`www.regeneron.com.
`
`About Bayer HealthCare
`
`The Bayer Group is a global enterprise with core competencies in the fields of health care, agriculture and high-tech materials.  Bayer HealthCare, a
`subgroup of Bayer AG with annual sales of EUR 18.6 billion (2012), is one of the world's leading, innovative companies in the healthcare and medical
`products industry and is based in Leverkusen, Germany.  The company combines the global activities of the Animal Health, Consumer Care, Medical
`Care and Pharmaceuticals divisions.  Bayer HealthCare's aim is to discover, develop, manufacture and market products that will improve human and
`animal health worldwide.  Bayer HealthCare has a global workforce of 54,900 employees ( Dec 31, 2012) and is represented in more than 100
`countries.  More information at www.healthcare.bayer.com.
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`Regeneron Forward-Looking Statements
`
`This news release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of
`Regeneron, and actual events or results may differ materially from these forward-looking statements.  Words such as "anticipate," "expect," "intend,"
`"plan," "believe," "seek," "estimate," variations of such words and similar expressions are intended to identify such forward-looking statements,
`although not all forward-looking statements contain these identifying words.  These statements concern, and these risks and uncertainties include,
`among others, the nature, timing, and possible success and therapeutic applications of Regeneron's products, product candidates, and research and
`clinical programs now underway or planned, including without limitation EYLEA®(aflibercept) Injection; unforeseen safety issues resulting from the
`administration of products and product candidates in patients, including serious complications or side effects in connection with the use of
`Regeneron's product candidates in clinical trials; the likelihood and timing of possible regulatory approval and commercial launch of Regeneron's
`late-stage product candidates and new indications for marketed products, such as the application of EYLEA® (aflibercept) Injection in the treatment of
`Diabetic Macular Edema; ongoing regulatory obligations and oversight impacting Regeneron's research and clinical programs and business;
`determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or
`commercialize Regeneron's products and product candidates; competing drugs and product candidates that may be superior to Regeneron's products
`and product candidates; uncertainty of market acceptance and commercial success of Regeneron's products and product candidates; the ability of
`Regeneron to manufacture and manage supply chains for multiple products and product candidates; coverage and reimbursement determinations by
`third-party payers, including Medicare and Medicaid; unanticipated expenses; the costs of developing, producing, and selling products; the ability of
`Regeneron to meet any of its sales or other financial projections or guidance and changes to the assumptions underlying those projections or
`guidance; the potential for any license or collaboration agreement, including Regeneron's agreements with Sanofi and Bayer HealthCare, to be
`cancelled or terminated without any further product success; and risks associated with third party intellectual property and pending or future litigation
`relating thereto.  A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities
`and Exchange Commission, including its Form 10-K for the year ended December 31, 2012 and its Form 10-Q for the quarterly period ended
`September 30, 2013.  The reader is cautioned not to rely on any forward-looking statements made by Regeneron.  Regeneron does not undertake any
`obligation to update publicly any forward-looking statement, including without limitation any financial projection or guidance, whether as a result of new
`
`Samsung et al. v. Regeneron IPR2023-00884
`Regeneron Pharmaceuticals, Inc. Exhibit 2106 Page 2
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`information, future events, or otherwise.
`
`Your Investor Relations Contact at Regeneron:
`Manisha Narasimhan, Ph.D. Tel. 914.847.5126
`E-Mail: manisha.narasimhan@regeneron.com
`
`Your Media Contact at Regeneron:
`Sandy Sexton, Tel. 914.847.3358
`E-Mail: sandra.sexton@regeneron.com
`
`SOURCE Regeneron Pharmaceuticals, Inc.
`
`News Provided by Acquire Media
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`Samsung et al. v. Regeneron IPR2023-00884
`Regeneron Pharmaceuticals, Inc. Exhibit 2106 Page 3
`
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